MajesTEC-9: A randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.
Cyrille Touzeau, Vânia TM Hungria, Divaya Bhutani, Ola Landgren, Diego Vieyra, Yue Guo, Raluca Verona, Xin Miao, Mia Qi, Latisha Watkins, Priya Shah, Katherine Chastain, Ming Qi, Hang Quach
Abstract
TPS8067 Background: Despite the advance in therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) over recent years, there remains a significant unmet medical need for new, well-tolerated therapies in earlier lines for patients who have previously received an anti-CD38 monoclonal antibody and lenalidomide. Teclistamab is the first B-cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of triple class-exposed RRMM. Teclistamab redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. MajesTEC-9 (NCT05572515) is a phase 3, randomized, open-label, multicenter study comparing teclistamab with investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with RRMM. Methods: Patients aged ≥18 years with RRMM (International Myeloma Working Group [IMWG] criteria) must have evidence of progressive disease or failure to achieve a response to last line of therapy and an Eastern Cooperative Oncology Group performance status score of 0–2. All patients must have received 1–3 prior lines of therapy, including ≥2 consecutive cycles of an anti-CD38 monoclonal antibody and ≥2 consecutive cycles of lenalidomide. Those treated with prior BCMA-directed therapy will be excluded. Approximately 590 patients will be randomized 1:1 to receive either teclistamab (28-day cycles) or PVd (21-day cycles) or Kd (28-day cycles). Stratification factors include investigator’s choice of PVd or Kd, stage of disease, number of prior lines of therapy, and anti-CD38 monoclonal antibody refractory status. Treatment will continue until disease progression, death, intolerance, withdrawal of consent, or end of study, whichever occurs first. The primary endpoint is progression-free survival (IMWG 2016 criteria); secondary endpoints include overall response rate, duration of response, and overall survival. Adverse events (AEs) will be graded by Common Terminology Criteria for AEs v5.0; cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome will be graded by American Society for Transplantation and Cellular Therapy criteria. The study opened in January 2023 and enrollment is ongoing. Clinical trial information: NCT05572515 .